The objectives of the proposed project are to identify the chemical structure of an isolated cystic fibrosis (CF) factor (mol. wt. 400) that is associated with a peptide (mol. wt. ca. 7000) in order to define its biochemical role in the pathophysiology of CF. The isolated salivary CF factor-peptide complex is specific to CF when measured by its inhibition of glycogen debranching enzyme and is not found in normal individuals or non-CF individuals with the organ pathologies associated with CF: chronic respiratory disease, pancreatic insufficiency, liver dysfunction, diabetes and elevated sweat electrolyte levels. The levels of CF factor-peptide complex found in homozygotes and heterozygotes show an autosomal recessive pattern when compared to normals indicating that the isolated material is related in some way to the genetic lesion in CF. In addition to inhibiting purified glycogen debranching enzyme, the CF factor is an even more potent inhibitor of purified glycogen phosphorylase and glycogen synthase. Kinetic evidence indicates that the CF factor inhibits these enzymes involved in glycogen metabolism by binding to their respective glucose binding sites. The CF peptide alone is inactive in all systems tested thus far but is probably related to the abnormal gene product. Glycogen isolated form the liver and muscle of children with CF was found to be normal in structure and amount indicating that the factor exerts no abnormal effect on glycogen metabolism intracellularly. The specific aims of this proposal are 1) To identify the chemical structure of the dissociated CF factor; 2) to quantitatively verify the specificity of the factor to CF; and 3) to devise a chemical or biochemical means of detecting the factor in CF heterozygote and homozygote patient materials.